The lining of the small intestine plays a particularly important role in the health and well being of an individual. It represents the major interface for nutrient uptake in the human body. The majority of energy uptake is through the brush border lining the small intestine. The surface area of the brush border is maximised by structures known as villi that protrude into the gut lumen.
Serious health ramifications can result should the functioning surface area of the brush border be significantly reduced, for example, by reason of the elaboration of the villi being reduced or by reason of damage to the enterocytes lining the brush border.
Damage to the small intestinal tract can be occasioned in any number of ways. For example, damage may result from an infection by a pathogen, or by conditions such as Crohn's disease, Coeliac disease and Diabetes. Alternatively, various treatments might occasion damage, for example, by the use of bactericides such as certain antibiotics or more usually by the application of anticancer treatments the enterocytes being particularly prone to the latter two as a result of their rapidly dividing nature.
The degree of enterocyte damage can be modulated for any of the above conditions, for example, by altering the severity of the treatment undertaken or by administering palliative agents. Such remedial action is currently not taken until manifestation of physiological symptoms resulting from an impairment of the brush border. Given that in many cases the subjects concerned are already under considerable stress it is highly desirable to address such potential failure as early as possible more particularly before the onset of such a failure. This therefore requires a suitable diagnostic method that might be predictive of such failure.
Currently the method used for definitive diagnosis of small intestinal damage and dysfunction is by biochemical and histological analysis of small bowel biopsy. The major disadvantages of this approach are (a) the invasiveness of taking a biopsy and (b) the extrapolation of information on enzyme activity and damage to the intestine from a small sample site to the entire small intestine. The latter assumes that conditions affecting the small intestine produce a uniform response throughout, however it is known that many conditions are focal in nature. This method is simply impractical to perform on a repeated basis.
Breath hydrogen tests are taken as a measure of small intestine malabsorption, and are an alternate approach to assessing damage to the small intestine. Breath hydrogen results from fermentable material being malabsorbed in the small intestine and presented to the colon for fermentation by microflora present in the large intestine. Thus reduction in the surface area of the small intestine or loss of enzyme activity will result in passage of digestible sugars (for example sucrose) to the colon and subsequent H2 production indicating problems with the small intestine. However the test is only appropriate if hydrogen-producing bacteria are present in the colon. It is thought that there is a significant proportion of human and animal populations (estimated at up to 20%) that do not have hydrogen producing bacteria resident in the large intestine. This then creates the potential for false negatives. In addition such tests are qualitative only and therefore do not give an estimate of the degree of damage or dysfunction that is present. These are major limitations of the clinical usefulness of the breath hydrogen test.
A third test that allows an assessment of the integrity of the small intestine is the sugar absorption test (SAT). The SAT measures the appearance of certain sugars in the urine (e.g. lactulose, rhamnose and sucrose). These are indicative of a damaged small intestine lining. SAT's are currently used in a limited fashion to assess intestinal permeability as a measure of the integrity of the small intestinal lining. Although these tests offer the advantage of being non-invasive they only test for one specific component of the small intestinal structure and function, that being the ability to maintain an impermeable barrier separating the contents of the gastrointestinal tract from the systemic system. The main disadvantages of SAT's are (a) the low diagnostic specificity (b) difficulty in performing the tests in the young, and (c) analysis of urinary excretions of the ingested probes involves intricate multi-step protocols which are difficult to perform.